From:  Vinyl sulfones: selective and tunable covalent warheads against challenging enzyme targets

 Vinyl sulfone inactivators of C. albicans ASADH [13, 14].

R1R2Ki (µM)kinact (min–1)kinact/Ki (M–1 s–1)
Methyl4-Pyridinyl5.690.24690
Methyl5-Nitrothiophene2.101.028,100
Methyl2-Quinoline0.960.6711,600
Methyl5-Isoquinoline0.650.7318,700
MethylAlanyl7.60.25550
BenzylAlanyl1.80.273,000
IsopropylAlanyl0.760.266,000
CyclopropylAlanyl0.390.3113,000

These compounds each functioned as irreversible inactivators of the ASADH isolated from Candida albicans (C. albicans), a pathogenic fungal species. Changes in the identity of R2 result in higher affinity, increased inactivation rates, and improvements in the ratio of inactivation rate (kinact) to affinity (Ki) that serves as a measure of covalent inactivator efficiency (Table 1, top). Further increases in target affinity are observed with changes to R1 (Table 1, bottom). ASADH: aspartate β-semialdehyde dehydrogenase.